Hadoxetic acid - instructions for use, doses, side effects, contraindications

Clinical and pharmacological group: & nbsp

Magnetic resonance contrast media

Included in the formulation

Primovist®

solution in / in

Bayer Pharma AG Germany

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

V.08.C.A Paramagnetic contrast media

Pharmacodynamics:The drug in the body is presented as an active substance: the disodium salt of gadoxetic acid. This salt has high hydrophilic properties and solubility. The ethoxymethyl group in the compound determines the lipophilic properties of the compound. At T₁-weighted scanning during magnetic resonance imaging the gadolinium ion shortens the spin-lattice relaxation time, leading to an increase in the signal intensity and, thereby, to a contrast enhancement of the region of interest. When using T₂-weighted pulse sequences, the induction of local non-homogeneity of the magnetic field under the influence of the strong magnetic moment of gadolinium at its high concentration (for example, with bolus administration) leads to a change in the signal from the tissues (the contrasting effect). The drug gadoxetic acid makes it possible to identify focal liver formations at magnetic resonance imaging, to obtain additional data on their character and thus increase the reliabilitydiagnosis.

Pharmacokinetics:After intravenous administration, the active substance quickly penetrates into the interstitial space. The disodium salt of gadoxetic acid does not pass through the unchanged blood-brain barrier and, in trace amounts, penetrates the placental barrier, is rapidly excreted from the fetal organism.

The half-life of the drug from serum is 1 hour, and does not significantly depend on the dose administered. Up to a dose of 0.4 ml / kg (0.1 mmol / kg) of body weight, the pharmacokinetics of hadoxetic acid is linear.

Gadoxetic acid (or rather, disodium salt) is unchanged in the form of a liver and kidneys in a ratio of 1: 1.

Peculiarities of pharmacokinetics in patients with impaired hepatic and renal function

Half-life is slightly increased in patients with violations of liver function of any severity. In patients with renal insufficiency, especially those in need of hemodialysis, the half-life of the drug is markedly increased.

Indications:Hadoxetic acid is used to increase the contrast when performing T₁-weighted magnetic resonance imaging of the liver in order to identify local lesions inadults, as well as their number, size, distribution by segments of the liver and so on.

ICD-10

XXI.Z00-Z13.Z03 Medical surveillance and evaluation in case of suspected disease or pathological condition

XXI.Z00-Z13.Z03.8 Observation for suspected other diseases and conditions

XXI.Z00-Z13.Z03.1 Observation for suspected malignant tumor

Contraindications:Hypersensitivity to the drug; pregnancy and the period of breastfeeding; children under 18 years of age (safety not studied).

Carefully:If kidney function is impaired, gadoxetic acid should be used only after a thorough examination and an assessment of the benefit-risk relationship for the patient.

Clinical data on patients with cardiovascular diseases are limited. Some studies reported a transient increase in the QT interval without any adverse reactions.

Special care is needed when using gadoxetic acid in patients with a history of allergic anamnesis (in particular, reaction to contrast agents in the past).

Pregnancy and lactation:Do not use during pregnancy if there is no obvious clinical need, exceeding the potential risk to the fetus. Action category for fetus by FDA - S.Well-controlled studies in humans have not been conducted. In animal experiments, the drug did not cause teratogenic and embryotoxic effects.

It is not known whether the active substance is excreted in human milk. In animal studies, it has been proven that gadoxetic acid in the minimum volume (0.5% of the administered dose) penetrates the breast milk of rats. After the drug is administered for 24 hours, it is necessary to stop lactation.

Dosing and Administration:The maximum single dose, well tolerated by people, according to the study - 0.4 ml / kg body weight (100 μmol / kg). The maximum daily dose of the drug can not be determined because of its use.

The ready-to-use solution is introduced at a rate of 2 ml / min.

The standard concentration of the drug in the solution is 0.25 mmol / l. Enter by intravenous bolus injection. The recommended dose is 25 μmol / kg of body weight to adults.

For children and adolescents under the age of 18, the drug is contraindicated.

Application in elderly patients

Use in patients older than 75 years has not been systematically studied. Although there is no data on the need to reduce the dosage of the drug in the elderly, more careful monitoring of their condition is necessary.Most elderly people have certain diseases of the cardiovascular system and often have a reduced renal function.

Side effects:From the side of the central nervous system: headache, dizziness, paresthesia, taste perversion, parosmia.

From the cardiovascular system: increased blood pressure, hot flashes, ECG - rarely prolongation of the QT interval.

From the digestive system: nausea, abdominal pain, vomiting, dry mouth, increased salivation.

From the sense organs: a violation of taste sensations, parosmia.

From the respiratory system: dyspnoea.

Dermatological reactions: skin itching, rash, maculopapular rash, increased sweating.

Allergic reactions: very rarely - anaphylactoid reactions, anaphylactic shock.

On the part of the body as a whole: chills, pain, back and chest pain, asthenia, general malaise, weakness, heat sensitivity.

Change in laboratory indicators: less than 1% - reversible (within 1-4 days) an increase in the iron and bilirubin content in the serum.

Overdose:Based on the studies of acute toxicity of gadoxetic acid in animals, there is no risk of acute intoxication with the use of the drug.The goals of therapy with a possible overdose are maintenance of vital functions, rapid administration of symptomatic therapy. The drug can and must be removed from the body by hemodialysis as soon as possible.

Interaction:Clinically Significant Interactions

Anionic preparations that are predominantly secreted with bile (such as rifampicin) can compete with gadoxetic acid for biliary excretion. In the experiment it was proved that the antibiotics of the rifamycin group block the absorption of the liver of gadoxetic acid. This leads to a decrease in its contrasting properties.

With increasing concentrations of bilirubin or ferritin in plasma and extracellular fluid, the contrasting properties of gadoxetic acid decrease.

When determining the iron content in the serum by complexometric methods, it is possible to obtain false values due to the free ligand of gadoxetic acid.

Due to the lack of compatibility testing, it is not recommended to mix gadoxetic acid with any other medicines.

Special instructions:There are data on the development of nephrogenic systemic fibrosis after the use of contrast agents,containing gadolinium in patients with severe renal dysfunction and in patients with acute renal insufficiency of any severity due to hepatorenal syndrome or perioperative period during liver transplantation. With this in mind, if kidney function is impaired, gadoxetic acid should be used only after a thorough examination and an assessment of the benefit-risk relationship for the patient.

After the introduction of gadoxetic acid, allergic reactions are possible up to anaphylactic shock, as well as manifestations of idiosyncrasy from the side of the cardiovascular, respiratory system and skin reactions. Considering this, after the procedure, it is recommended to monitor the patient's condition for at least 30 minutes.

The drug is administered only intravenously. With intramuscular injection, local tissue reactions are possible up to necrosis. Avoid intramuscular injection!

Instructions

Hadoxetic acid (Acidum gadoxeticum)